Evaluation of the Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
First received: June 27, 2012
Last updated: July 11, 2015
Last verified: June 2015
This study investigated the effects of LCZ696 on insulin sensitivity, lipolysis, and oxidative metabolism in obese hypertensive subjects.

Condition Intervention Phase
Concurrent Obesity
Drug: LCZ696
Drug: amlodipine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: A Randomized, Double-blind, Parallel Group Study to Evaluate Metabolic Effects of LCZ696 and Amlodipine in Obese Hypertensive Subjects

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in Insulin Sensitivity Index [ Time Frame: baseline, 8 weeks ] [ Designated as safety issue: No ]
    The insulin sensitivity index was assessed by hyperinsulinemic euglycemic clamp (HEGC). A positive change from baseline indicates improvement.

Secondary Outcome Measures:
  • Local Adipose Tissue Lipolysis, Glycerol Concentrations [ Time Frame: 57 days ] [ Designated as safety issue: No ]
    Lipolysis was assessed through subcutaneous adipose tissue microdialysis. The actual measure type is adjusted geometric mean.

  • Oxidative Metabolism [ Time Frame: 57 days ] [ Designated as safety issue: No ]
    Oxidative metabolism was assessed by indirect calorimetry.

  • Number of Participants With Adverse Events, Serious Adverse Events and Deaths [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Adverse event monitoring was conducted throughout the study.

Enrollment: 98
Study Start Date: October 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LCZ696
LCZ696 400 mg plus placebo to amlodipine once daily for 8 weeks
Drug: LCZ696
LCZ696 was provided as 400 mg tablets.
Drug: Placebo
Matching placebo to LCZ696 and amlodipine.
Active Comparator: amlodipine
amlodipine 10 mg plus placebo to LCZ696 once daily for 8 weeks
Drug: amlodipine
amlodipine was provided as 5 mg tablets.
Drug: Placebo
Matching placebo to LCZ696 and amlodipine.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Written informed consent must be obtained before any study assessment is performed.
  • Males and females of non-childbearing potential ≥ 18 years of age.
  • Subjects with mild to moderate essential hypertension,

    • Untreated subjects must have a mean seated SBP (msSBP) ≥ 130 mmHg and < 180 mmHg at screening.
    • Pre-treated subjects must have a msSBP ≤ 160 mmHg at screening and < 180 mmHg at the end of the washout period.
  • Waist circumference ≥ 102 cm (men) and ≥ 88 cm (women);

Exclusion criteria:

  • Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer; or longer if required by local regulations.
  • History of angioedema, drug-related or otherwise
  • History of hypersensitivity to LCZ696, amlodipine, or drugs of similar chemical classes.
  • Severe hypertension (grade 3 of WHO classification; msDBP ≥100 mmHg and/or msSBP ≥ 180 mmHg) at screening or at the end of the washout period.
  • Type 1 or Type 2 diabetes mellitus.
  • Dyslipidemia requiring pharmacological therapy with a fibrate or nicotinic acid.
  • Concomitant use of anti-hypertensives, anti-diabetics, or drugs with effects on glucose or lipid metabolism for the duration of the study.

Other protocol defined inclusion/exclusion criteria may apply

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01631864

Novartis Investigative Site
Hannover, Germany, 30625
Novartis Investigative Site
Neuss, Germany, 41460
Novartis Investigative Site
Maastricht, Netherlands, 5800
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01631864     History of Changes
Other Study ID Numbers: CLCZ696B2207, 2012-002606-40
Study First Received: June 27, 2012
Results First Received: July 11, 2015
Last Updated: July 11, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices (BfArM)
Netherlands: Medicines Evaluation Board (MEB)

Keywords provided by Novartis:
Hypertension, obesity, insulin sensitivity, lipolysis, LCZ696

Additional relevant MeSH terms:
Antihypertensive Agents
Calcium Channel Blockers
Cardiovascular Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 30, 2015